Methods and compositions for the treatment of chronic pain using dhea and derivatives thereof

Abstract

The invention relates to the treatment of chronic pain using DHEA or derivatives thereof either alone or in combination with at least one other drug. The invention also includes compositions comprising DHEA or a derivative thereof and a second drug.

1 . A method for treating chronic pain in a patient comprising administering an effective chronic pain-treating dose of a composition comprising DHEA of the formula:  
     
       
         
         
             
             
         
       
     
     or a prodrug, salt, isomer, analog, metabolic precursor or a metabolic or chemical derivative thereof.  
   
   
       2 . The method of  claim 1 , wherein the composition is administered orally.  
   
   
       3 . The method of  claim 1 , wherein the composition is administered transdermally.  
   
   
       4 . The method of  claim 1 , wherein the chronic pain is selected from an idiopathic or undiagnosed or an undiagnosible disease, disorder or condition, or wherein the chronic pain is selected from any one of: myofascial pain syndrome, trigger points, tender points, thorasic outlet syndrome, complex regional pain syndrome, reflex sympathetic dystrophy (RSD),sympathetically maintained pain (SMP), diabetic neuropathy; chronic pain associated with traumatic injury to the peripheral nervous system; chronic pain resulting from herpes zoster (also known as shingles, or post-herpetic neuropathy) or similar infections that attack and damage nerve fibers or endings; post-operative pain, which arises after surgery and then lingers far beyond a normal convalescent period; pain associated with nerve and root damage, such as pain associated with peripheral nerve disorders, including, nerve entrapment and brachial plexus avulsions, amputation, peripheral neuropathies, tic douloureux, atypical facial pain, nerve root damage, and arachnoiditis, in which an amputee suffers from feelings of pain or discomfort that seems to originate in the missing limb (“phantom limb” pain); pain associated with carcinoma, often referred to as cancer pain; central nervous system pain, including pain due to spinal cord or brain stem damage; low back pain; sciatica; headache, including migraine, chronic tension headache, cluster headache, temporomandibular disorder (TMJ) pain and maxillary sinus pain; complex regional pain syndromes, including reflex sympathetic dystrophy and causalgia, or from burn injury.  
   
   
       5 . The method of  claim 1 , wherein the chronic pain is selected from: 
 (a) neuropathic pain;    (b) hyperesthesia;    (c) allodynia;    (d) hyperalgesia;    (e) deafferentation pain;    (f) sympathetically maintained pain; or    (g) non-nociceptive chronic pain.    
   
   
       6 . The method of  claim 1 , wherein the pain is caused by: trigger points, trigger points and tender points, trigger points but not tender points, tender points, or tender points but not trigger points.  
   
   
       7 . The method of  claim 1 , wherein the chronic pain is myofascial pain syndrome but not fibromyalgia with myofascial pain syndrome.  
   
   
       8 . The method of  claim 1 , wherein the composition is administered orally  
   
   
       9 . The method of  claim 1 , wherein DHEA or derivative thereof is administered transdermally.  
   
   
       10 . A method for treating chronic pain, comprising the step of administering, to a mammal suffering from chronic pain, a drug composition combination comprising: (a) a first drug which is DHEA or a prodrug, salt, isomer, analog, or derivative thereof, and which is pharmaceutically acceptable, and, (b) a second drug, wherein the second drug is: (i) useful for the treatment of chronic pain when used alone, or (ii) not effective for treating chronic alone, but is more effective then the first drug alone when used in combination with the first drug, or (iii) known to reduce chronic pain when used alone, and wherein the first and second drugs are administered at dosages which, when combined, provide synergistic and therapeutically effective relief from chronic pain.  
   
   
       11 . The method of  claim 10 , wherein the combination either provides relief that lasts longer than comparable pain relief provided by either drug alone or causes lower levels of adverse side effects that the second drug administered by itself would cause at a dosage which provides comparable relief from chronic pain.  
   
   
       12 . The method according to  claim 10 , wherein the second drug is selected from propoxyphene; meperidine; hydromorphone; hydrocodone; morphine, codeine; tramodol; ziconotide; dextromethorphan; eliprodil; ifenprodil; a cox-2 inhibitor; rofecoxib; celecoxib; salycylic acid; diclofenac; oxicams; indomethacin; ibuprofen; naproxen; gabapentin; carbamazepine; pregabalin; lamotrigine; topiramate; clonazepam; valproic acid; elitriptan; sumatriptan; rizatriptan; zolmitriptan; naratriptan; flexeril; carisoprodol; robaxisal; norgesic; dantrium; a benzodiazepine; diazepam; fentanyl; mephobarbital; pentobarbital sodium; oxycodone hydrochloride; tramadol hydrochloride; chlordiazepoxide; alprazolam; lorazepam; acetominophen; nitrous oxide; halothane; lidocaine; etidocaine; ropivacaine; chloroprocaine; sarapin; bupivacaine; capsaicin; desipramine; a tricyclic antidepressant; nortriptyline; amitriptyline; doxepin, perphenazine, protriptyline, tranylcypromine, clonidine; anti-arrythmics mexilitene; an antihistamine; diphenhydraimine; hydroxyzine; caffeine; prednisone; methyl-prednisone; decadron; selective serotonin reuptake inhibitor (SSRI); paroxetine; sertraline; fluoxetine; citalopram; bupropion; levodopa; and pharmacologically acceptable prodrugs, salts, isomers, analogs and derivatives thereof.  
   
   
       13 . A composition for treating chronic pain, comprising a first drug which is DHEA or a prodrug, salt, isomer, analog, metabolic precursor or a metabolic or chemical derivative thereof; and a second drug, wherein the second drug is: (i) useful for the treatment of chronic pain when used alone, or (ii) not effective for treating chronic alone, but is more effective then the first drug alone when used in combination with the first drug, or (iii) known to reduce chronic pain when used alone, and wherein the first and second drugs are administered at dosages which, when combined, provide synergistic and therapeutically effective relief from chronic pain.  
   
   
       14 . The composition of  claim 13 , wherein the second drug is selected from propoxyphene; meperidine; hydromorphone; hydrocodone; morphine, codeine; tramodol; ziconotide; dextromethorphan; eliprodil; ifenprodil; a cox-2 inhibitor; rofecoxib; celecoxib; salycylic acid; diclofenac; oxicams; indomethacin; ibuprofen; naproxen; gabapentin; carbamazepine; pregabalin; lamotrigine; topiramate; clonazepam; valproic acid; elitriptan; sumatriptan; rizatriptan; zolmitriptan; naratriptan; flexeril; carisoprodol; robaxisal; norgesic; dantrium; a benzodiazepine; diazepam; fentanyl; mephobarbital; pentobarbital sodium; oxycodone hydrochloride; tramadol hydrochloride; chlordiazepoxide; alprazolam; lorazepam; acetominophen; nitrous oxide; halothane; lidocaine; etidocaine; ropivacaine; chloroprocaine; sarapin; bupivacaine; capsaicin; desipramine; a tricyclic antidepressant; nortriptyline; amitriptyline; doxepin, perphenazine, protriptyline, tranylcypromine, clonidine; anti-arrythmics mexilitene; an antihistamine; diphenhydraimine; hydroxyzine; caffeine; prednisone; methyl-prednisone; decadron; selective serotonin reuptake inhibitor (SSRI); paroxetine; sertraline; fluoxetine; citalopram; bupropion; levodopa; and pharmacologically acceptable prodrugs, salts, isomers, analogs and derivatives thereof.  
   
   
       15 . The composition of  claim 13 , wherein the combination either provides relief that lasts longer than comparable pain relief provided by either drug alone or causes lower levels of adverse side effects that the second drug administered by itself would cause at a dosage which provides comparable relief from chronic pain.  
   
   
       16 . The method of  claim 6 , wherein the trigger point is located at a muscle or position selected from any 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; ornotmorethanl, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, of the following: Head and Neck Splenius, Splenius cervicis, semispinalis cervicis, rotatores, multifidi, Upper trapezius, Sternocleidomastoid, Clavicular, Sternal, Splenius capitis, Temporalis, masseter, medial and lateral pterygoid, Shoulder, Thorax, and Arm, Anterior serratus, Pectoralis major, and minor, Levator scapulae, Infraspinatus, Supraspinatus, Back and Buttock, Quadratus lumborum, Iliocostalis, Gluteus maximus, Thigh, Leg, and Foot, Quadriceps femoris, Rectus femoris, Vastus intermedius, Vastus medialis, Biceps femoris, Gastrocnemius, Soleus.  
   
   
       17 . Use of the composition according to  claim 1  or  13  for the manufacture of a medicament for treating chronic pain.  
   
   
       18 . A medicament for treating chronic pain comprising a pharmaceutical compound which includes an active ingredient consisting of the composition of  claim 1  or  13 .  
   
   
       19 . A pharmaceutical composition for treating chronic pain comprising a pharmaceutically effective amount of the composition of  claim 1  or  13 .  
   
   
       20 - 25 . (canceled)  
   
   
       26 . The method of  claim 1 , wherein: 
 (a) said chronic pain is non-responsive to gabapentin;    (b) said chronic pain is partially responsive to a cox-2 inhibitor;    (c) said chronic pain is partially responsive to a tricyclic antidepressant;    (d) said patient has a lower than normal blood level of DHEA; or    (e) blood levels of DHEA are increased at least 3 fold after 3 months of treatment with DHEA.